Why does alcohol cause cardiomyopathy

In we updated the data on the ambivalent relationship between alcohol and the heart [ 19 ] and in added new evidence on a larger cohort of patients with different forms of cardiomyopathy and increased alcohol intake from the German competence network on heart failure [ 20 ]. This review revisits our past and deals with our current thinking on the epidemiology, pathophysiology, clinical characteristics, and treatments available for alcoholic cardiomyopathy. This review assembles and selects pertinent literature on the ambivalent relationship of ethanol and the cardiovascular system, including guidelines, meta-analyses, Cochrane reviews, original contributions, and data from the Marburg Cardiomyopathy registry.

Drinks as measures of alcohol are often given in ounces oz , whereby 1 oz equals Distilled spirits: 1. For more than years, alcoholic beverages have been consumed in multiple societies through the centuries and cultures. The name alcohol is much younger than the many beverages containing it. Pulverized antimony was used as eye shadow by Egyptian women and named al-Kol. In the 16th century Paracelsus Theophrastus Bombastus from Hohenheim used this term for distilled liquor and called it alcohol [ 15 ].

The beneficial cardiovascular effects of alcohol have been appreciated, e. So Hildegard von Bingen — , one of the most prominent mysticians of her time, recommended her heart wine as a universal remedy. One liter of wine was cooked for 4 min with 10 fresh parsley stems, 1 spoon of vinegar, and g honey and then filtered [ 11 ]. This recipe is still in use today. As early as , Wood incriminated alcohol as a cause of heart failure.

In , Friedrich reported idiopathic hypertrophy as associated with alcoholism. In , Walshe described myocardial cirrhosis in alcoholics, which includes a spectrum of hepatic derangements that occur in the setting of right-sided heart failure. Conversely cirrhosis fibrosis was found both in heart and liver. High cardiac output in patients with liver cirrhosis may have contributed to this cardiomyopathy in a vicious circle. Myofibers show partly hypertrophy and atrophy.

Fibrosis is present as reparative interstitial and perivascular fibrosis. With kind permission from H. Frenzel and B. Schwartzkopff [ 22 ]. In Munich, the annual consumption of beer reached l per capita and year in the last quarter of the 19th century. In , the pathologist and veterinarian Otto von Bollinger Fig.

For comparison, the mean annual beer consumption in Bavaria is nowadays estimated to be l and in the rest of Germany around l beer per person and year [ 24 ].

In , Maguire reported on 2 patients with severe alcohol consumption who benefitted from abstinence. He suggested that alcohol was poisoning the heart. In , Graham Steell, well known for the Graham Steell murmur due to pulmonary regurgitation in pulmonary hypertension or in mitral stenosis, reported 25 cases in whom he recognized alcoholism as one of the causes of muscle failure of the heart.

In his review article, Bridgen was the first to introduce the term alcoholic cardiomyopathy [ 27 ]. Thus, the concept of beriberi heart disease dominated thinking about alcohol and the heart for decades and caused many to doubt that alcohol was actually cardiotoxic [ 28 ]. But vitamin B1 thiamine deficiency is accompanied by an elevated cardiac output and diminished peripheral vascular resistance [ 29 , 30 ]. In contrast, alcoholic cardiomyopathy is characterized by a low cardiac output, associated with systemic vasoconstriction [ 4 ].

However, the high output state can lead to cardiac dilation, thus, representing a characteristic subentity of cardiomyopathy different from low output dilated cardiomyopathy.

Therefore, thiamine deficiency per se is just a historical nutritional anomaly in the history of alcoholic cardiomyopathy. In , the Manchester arsenic-in-beer epidemic was a serious food poisoning outbreak affecting several thousand people across the North-West and Midlands of England, with many cases proving fatal.

The arsenic had come from the glucose for which sulphuric acid was used in the sugar production process of a company in Leeds. Brewers had been using this sugar, thus, unknowingly poisoning the beer and as a result their customers for many years even prior to the epidemic [ 33 ]. Arsenic poising caused a multisystem disease in over cases with more than 70 deaths [ 34 ].

The syndrome included the usual signs and symptoms of arsenic poisoning, with skin, nervous system, and gastrointestinal manifestations. Unusual in arsenic poisoning, but especially prominent in this epidemic, were the cardiovascular findings. This outbreak had been the first known trace metal cardiotoxic syndrome.

In , the issue of arsenic in beer and wine was again prominent, when Mehmet Coelhan, a researcher at the Weihenstephan research center at the Technical University of Munich, reported at a meeting of the American Chemical Society that many of the nearly beers tested in Germany had trace amounts of arsenic. The source was identified to be the filter of choice for wine and beer, i.

The German word for it is Kieselguhr, a beige powder made up of the skeletons of diatoms. The trace amounts of arsenic have not been comparable to the arsenic-in-beer endemic in Manchester but may still reach up to times the amount admitted for arsenic in drinking water in the European Union and the US. In the mids, another unexpected heart failure epidemic among chronic, heavy beer drinkers occurred in two cities in the USA, in Quebec, Canada, and in Belgium.

It was characterized by congestive heart failure, pericardial effusion, and an elevated hemoglobin concentration. The explanation proved to be the addition of small amounts of cobalt chloride. Cobalt was used as a foam stabilizer by certain breweries in Canada and in the USA. In McDermott et al. Human pathology was first described by Bonefant et al. Animal models investigated ultrastructure [ 41 ] and treatment e. Removal of the cobalt additive ended the epidemic in all locations. Cobalt poisoning and alcohol together acted synergistically in these patients.

As the syndrome could be attributed to the toxicity of this trace element, the additive was prohibited thereafter. Not alcohol but cobalt itself recently caused severe heart failure in a year-old man, who was referred to the university hospital in Marburg to rule out coronary artery disease as the cause of his heart failure.

He had become almost deaf and blind, with fever of unknown cause, hypothyroidism, and enlarged lymph nodes. Both his hips had been replaced, the left side by a CoCrMo Protasul metal prosthesis. Remembering a similar case in an episode of the TV series Dr.

House , the team of J. One should note, however, that cobalt is needed in minute amounts of 0. The heart and liver interact in several different ways. Acute or chronic right heart failure leads to elevation of liver enzymes most likely due to liver congestion, whereas cirrhosis due to cardiac disease is infrequent.

Chronic liver disease such as cirrhosis may in turn affect the heart and the whole cardiovascular system, leading to a syndrome named cirrhotic cardiomyopathy CCM. Thus, CCM has been introduced as an new entity separate of the cirrhosis etiology. Increased cardiac output due to hyperdynamic circulation, left ventricular dysfunction systolic and diastolic , and certain electrophysiological abnormal findings are pathophysiological features of the disease.

In pathophysiological terms, heart failure in liver cirrhosis belongs to the hyperdynamic cardiomyopathies. As early as in , Lian [ 45 ] reported in middle-aged French servicemen during the first world war that heavy drinking could lead to hypertension.

It took almost 60 years before further attention was paid to the complex interaction between the heart and the peripheral vasculature in various cross-sectional and prospective epidemiologic studies, which have empirically confirmed this early report. One is aware today that alcohol may cause an acute but transient vasodilation, which may lead to an initial fall in blood pressure probably mediated by the atrial natriuretic peptide ANP [ 46 ]. But also short- and long-term pressor effects mediated by the renin—aldosterone system and plasma vasopressin have been described [ 47 , 48 ].

The long-term hypertensive effect of alcohol has been confirmed in many studies [ 49 — 52 ]. Remarkably, alcohol also interacts with brain stem receptors and exerts thereby central hypertensive effects [ 18 ]. There seems to be independence from adiposity, salt intake, education, smoking, beverage type wine, liquor, or beer , and several other potential confounders.

Clinical observation confirmed that several days to weeks of drinking show higher and weeks of abstinence lower pressures. Alcohol intake may also interfere with the drug and dietary treatment of hypertension. This altogether supports a causal relationship between alcohol consumption and a hypertensive state.

The landmark report of Urbano-Marquez et al. Further evidence came from data on acute alcohol effects [ 54 ] and from clinical observation [ 55 — 57 ]. After consumption of large quantities of alcohol over years the clinical picture of heavy alcohol drinkers could be indistinguishable from other forms of dilated or familial cardiomyopathy. Alcohol is still suspected to be the major cause or contributory factor of secondary nonischemic dilated cardiomyopathy being involved in up to one third of all cases of dilated cardiomyopathy [ 59 — 61 ].

In alcoholic cardiomyopathy, dilation and impaired contraction of the left or both ventricles is observed [ 4 ]. Thus, the diagnosis of alcoholic cardiomyopathy is still based on the coincidence of heavy alcohol consumption and a global myocardial dysfunction, which cannot be explained by any other underlying myocardial disease [ 64 ]. However, the prevalence of alcoholic cardiomyopathy may be underestimated, as autopsy findings reveal pathologic changes of the heart in individuals with no clinical symptoms [ 65 ], when analyzing in large cross-sectional studies.

Further evidence suggests that not only ethanol but also the first metabolite acetaldehyde may directly interfere with cardiac and skeletal muscle homeostasis [ 53 , 66 ]. In vitro studies have further elucidated the direct effect of ethanol on electromechanical coupling, indicating a decrease in myofilament—calcium sensitivity during alcohol consumption, changes in the transmembrane action potential, the amplitude of the cytosolic calcium transients, and the shortening of the action potential duration [ 67 — 71 ].

Isolated cardiomyocytes of alcohol-fed rats did not maintain ATP levels upon energy demand due to an inadequate increase in mitochondrial ATP-synthase activity, which led altogether to further myocyte loss [ 72 , 73 ]. Ultrastructural disarray of the contractile apparatus [ 74 ] is associated with a depressed myofibrillar and sarcoplasmic protein synthesis in cardiac muscle after ethanol exposure [ 75 — 77 ].

This reduces contractile cardiac filaments with subsequent negative inotropic effects on heart contractility [ 78 , 79 ]. An apoptotic effect of ethanol on cardiac muscle has also been described, which could be counteracted by insulin-like growth factor IGF -I [ 80 ] and confirmed in later studies [ 81 , 82 ]. In a study in rats that were fed with two different doses of alcohol 5 mM [low alcohol], mM [high alcohol] or in pair-fed nonalcohol controls for 4—5 months , caspase-3 activity as putative marker of apoptosis was decreased in the low alcohol diet, which went along with increased or normal contractility, whereas high doses of ethanol showed increased caspase activity, wall thinning, and a reduction of shortening velocity [ 83 ].

Of note, rats are a relatively alcohol resistant species. Alcohol abuse coinciding with myocarditis was reported in by McKenzie [ 26 ].

Perivascular increase of leukocytes and fibrosis, myocytes in variable sizes with some myocytolysis. Indirect immunofluorescent test. This may have to do with the susceptibility for infections due to a suppressed immune system in a compromised human host and also in experimental animal [ 85 ].

Ethanol can alter lymphocyte functions, inhibit neutrophil chemotaxis, and suppress the production of cytokines, which are involved in regulating acute inflammatory responses to infectious challenges [ 86 — 88 ]. Furthermore, autoimmunity and circulating autoantibodies seem to be associated in some patients with chronic alcohol consumption [ 16 , 20 , 84 ].

The beneficial heart wine as universal remedy in medieval ages by Hildegard von Bingen [ 11 ] found its later correlates in many observations at the beginning of modern medicine when coronary artery disease CAD and its risk factors and symptoms received more attention.

This observation led to the erroneous belief that alcohol is an immediate coronary vasodilator. Alcohol is not a direct coronary vasodilator [ 90 ]. Symptomatic relief of angina could be through the anesthetic effect of ethanol or through peripheral vasodilation, which could transiently reduce oxygen demand of the heart.

In the Irish physician Dr. This refers to the finding in the last century that moderate alcohol consumption could be the reason for the relatively low cardiovascular disease incidence in wine-drinking regions [ 92 ].

Renaud and de Lorgeril [ 93 ] suggested that the inhibition of platelet reactivity by wine may be one explanation for protection from CAD in France.

However, there was further evidence on this and other dietary mechanisms with the observation that France and Finland have similar intakes of cholesterol and saturated fat, but consumption of vegetables and vegetable oil containing monounsaturated and polyunsaturated fatty acids is greater in France than in Finland.

This inverse relation on mortality resembles in most population based studies a U- or J-shaped curve: Total abstinence has a slightly increased mortality when compared to low or moderate alcohol consumption. It is present in individuals with and without overt CAD, with diabetes, and with hypertension and has been underlined by a large number of studies [ 94 , 95 ]. The cardioprotective effect of alcohol can be attributed to the increase in total high-density lipoproteins HDL , and especially by an increase in subfractions HDL2 and HDL3, whereas established cardiovascular risk factors like low-density lipoproteins LDL or lipoprotein a are thought to be moderately decreased [ 96 ].

Moderate alcohol intake also exerts beneficial effects on the blood coagulation system. It leads to an increase of endogenous plasminogen activators [ 97 ], or a decrease in fibrinogen concentrations [ 98 ].

In the Caerphilly prospective heart disease study, platelet aggregation induced by adenosine diphosphate was also inhibited in subjects who drank alcohol [ 99 ]. Assessing differences between various forms of alcoholic beverages it should be noted that resveratrol leads in vitro to platelet inhibition in a dose-dependent manner [ ] and has shown effects on all-cause mortality in a community-based study [ ].

Polyphenols of red barrique wines and flavonoids have been shown to inhibit endothelin-1 synthase [ ] and PDGF-induced vasoproliferation thus also contributing to cardiovascular protection [ ]. As a net effect, negative inotropism may result and contribute to heart failure. Acute effects of alcohol can result in rhythm disturbances. Atrial fibrillation was the commonest manifestation, which resolved with abstinence.

Apart from direct cardiotoxicity, hypertension causing atrial stretch the arrhythmogenic potential of alcohol may come from the lowering the resting membrane potential [ ] and the prolongation of conduction [ ]. Studies of alcohol and stroke are complicated by the various contributing factors to stroke. Heavier drinkers are apparently at a higher risk of hemorrhagic stroke, whereas moderate drinking might be neutral or even result in a reduced risk of ischemic stroke.

Habitual drinkers often hide their alcohol dependence fairly effectively. They may admit drinking at social events but not the abuse in the first contact.

Patients with alcoholic cardiomyopathy, therefore, usually present with symptoms of heart failure, i. Echocardiography may reveal a mild or severe depression of cardiac function and ejection fraction or even show hypertrophy in the beginning [ ].

Heart failure symptoms may be due to early diastolic or to later systolic dysfunction. At later stages, due to atrial fibrillation, thrombi are not uncommon in the dilated atria. Mitral regurgitation is found in up to two thirds of cases [ ]. On ECG, unspecific abnormalities like complete or incomplete left bundle branch block, atrioventricular conduction disturbances, alterations in the ST segment, and P wave changes can be found comparable to those in idiopathic DCM [ ].

Although the severity of histological alterations on endomyocardial biopsy correlates with the degree of heart failure in one of our studies, biopsy is not in common use for prognostic purposes [ ]. Even the recovery after abstinence of alcohol is hard to predict based on morphometric evaluation of endomyocardial biopsies [ ].

Cardiac MRI may be helpful in the differential diagnosis to hypertrophic cardiomyopathy, storage diseases, and inflammatory cardiomyopathy.

For a comprehensive overview see Table 1 combined data from [ 6 , 8 , 24 , 28 ]. Measuring blood alcohol concentration in an acute intoxication gives baseline information but does not permit deductions to chronic misuse. Markers for chronic alcohol consumption rely on liver enzymes such as gamma-glutamyltransferase GGT [ ], glutamic oxalacetic transaminase GOT , and glutamic pyruvic transaminase GPT.

An excellent marker is carbohydrate deficient transferrin CDT , which best detects chronic alcohol consumption alone [ , ] or in combination with the other markers such as GGT [ 8 , ]. Markers such as ethyl sulphate, phosphatidyl ethanol, and fatty acid ethyl esters are not routinely done.

For a comprehensive overview see Table 2 with combined data from [ 6 , 8 , 24 , 28 ]. There seem to be a few common manifestations of alcoholic cardiomyopathy that will help you detect it relatively early.

When this happens, the symptoms often become similar to those of heart disease. Several of the possible side effects of alcoholic cardiomyopathy that could be discovered through a surgical test are stated below.

The main side effects includes:. Eventually, a certain incidence of heart disease caused by alcoholic cardiomyopathy that a careful analysis may find include:. Most of your tissues, like your heart, are harmed by alcoholic cardiomyopathy.

Alcohol intoxication reduces and affects the cardiovascular system over time. It makes it harder for the heart to pump blood properly. The heart is stretched and swollen as a result of this.

Owing to the damage and pressure, the blood vessels and internal organs can gradually stop working correctly. As there are many capillaries and sensitive nerves that cannot take the pressure and end up bursting or being worn out of alcoholic cardiomyopathy.

All these helping structures when disrupted results in malfunctioning of the main veins and arteries. The function of pumping blood requires strength and this strength comes from the healthy inner walls of veins and arteries of the heart. However, alcohol consumption specifically regular and excessive consumption can make them weak and lose all their elasticity and strength disabling them from performing their main function of pumping blood to the whole body.

After the addiction has progressed to a severe medical condition, such as alcoholic cardiomyopathy, certain people with substance dependency problems refuse to get treatment. As old age goes, individuals must first recognize that they also have a condition while addressing their dependence and embarking on a safe and complete rehabilitation path. Having others admits they have a concern is always the most challenging aspect. Some who matter for an alcoholic who may very well have alcoholic cardiomyopathy may stage action in front of the alcoholic and those who support their corrective measures.

An intervention involves people who are concerned for the person in a similar room as alcoholic. During that time, family members and friends question the harmful impact of alcohol on that particular person and his surrounding environment.

An operation requires diligent preparation, the acquisition of pertinent details, the creation of possible outcomes by each family if medication is refused, including joining with both the person who suffers and ensure a satisfactory rehabilitation.

An intervention typically ends with family members arguing with both the alcoholic cardiomyopathy to admit their illness and seek help right away.

The patient may become violent, angry, angry, angry, unhappy, uncommunicative, and otherwise adversely affected by an action. That diagnosis for someone infected with alcoholic cardiomyopathy and has extensive heart failure is usually wrong.

The very first phase in the therapy of alcoholic cardiomyopathy is to abstain from eating alcohol entirely. Your physician will support you in preventing the effects of alcohol withdrawal. To help lower the blood pressure, the doctor can prescribe ACE inhibitors and beta-blockers. If your heart is badly injured, your doctor can suggest an injectable stethoscope or stent to help your heart work properly.

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